The uncertainty of a result is an important measure of the quality of the result. The terms “uncertainty of a result” and “uncertainty of a measurement” comprise an evaluation of the precision of the method leading to the result or measurement. All parts of the method or measurement, which possibly influence the quality, need to be considered. In the instance of a clinical analysis or assay, information about the uncertainty of the results should preferably be available.
The European co-operation for Accreditation, EA, have designated GUM (Guide to the Expression of Uncertainty in Measurement, International Organisation of Standardisation, ISO, Genève, 1995) as the “master document” for estimation of uncertainty of measurement. This document is incorporated herein by reference in its entirety.
PCT/SE03/00919 relates to a micro fluidic system comprising a substrate and provided on said substrate there is at least one flow path comprising a plurality of micro posts protruding upwards from said substrate, the spacing between the micro posts being small enough to induce a capillary action in a liquid sample applied, so as to force said liquid to move. It is disclosed that the device can comprise a denser zone which can act as a sieve preventing for instance cells to pass. There is also disclosed an embodiment with microstructures where the shape, size and/or center-to-center distance forms a gradient so that the movement of a fraction of the sample, a cell type or the like can be delayed and optionally separated.
PCT/SE2005/000429 shows a device and method for the separation of a component in a liquid sample prior to the detection of an analyte in said sample, wherein a sample is added to a receiving zone on a substrate. The substrate further optionally comprises a reaction zone, a transport or incubation zone connecting the receiving and reaction zone, respectively, forming a flow path on a substrate. The substrate is a non-porous substrate, and at least part of said flow path consists of areas of projections substantially vertical to the surface of said substrate, and having a height, diameter and reciprocal spacing such, that lateral capillary flow of said liquid sample in said zone is achieved, and where means for separation are provided adjacent to the zone for receiving the sample. There is disclosed an embodiment where red blood cells are removed.
WO 2005/118139 concerns a device for handling liquid samples, comprising a flow path with at least one zone for receiving the sample, and a transport or incubation zone, said zones connected by or comprising a zone having projections substantially vertical to its surface. The device is provided with a sink with a capacity of receiving said liquid sample, said sink comprising a zone having projections substantially vertical to its surface, and said sink being adapted to respond to an external influence regulating its capacity to receive said liquid sample. It is disclosed that the device can be used when particulate matter, such as cells, is to be removed from the bulk of the sample. It is stated that red blood cells can be separated without significant rupture of the cells.
In lateral flow assay devices in which the result is read in a reaction zone, there may under certain circumstances occur variations in the result due to variations in, for instance, the deposition of reagents on the assay device, binding of reagents to the assay device, drying of the reagents on the assay device, and reading of a signal from the assay device.
WO 2008/137008 to Claros Diagnostics Inc. discloses a device which has a reagent arranged in a microfluidic channel of a microfluidic system of a substrate. A fluidic connector includes a fluid path with a fluid path inlet and a fluid path outlet connected to an outlet and an inlet of microfluidic channels to allow fluid communication between the path and the channels, respectively. The path contains a sample or the reagent arranged prior to connection of the connector to the substrate. There are disclosed embodiments where the reaction area comprises at least two meandering channel regions connected in series. It is disclosed that detection zones can be connected in series. It is disclosed that the detected signal can be different at different portions of a region. A problem in WO 2008/137008 is that this device is still susceptible to variations in factors such as deposition of reagents on the assay device, binding of reagents to the assay device, drying of the reagents on the assay device, and reading of a signal from the assay device.
US 2008273918 discloses fluidic connectors, methods, and devices for performing analyses (e.g., immunoassays) in microfluidic systems.
WO 01/02093 discloses a detection article, including at least one fluid control film layer having at least one microstructured major surface with a plurality of microchannels therein.
Although the state of the art lateral flow assay devices can be used satisfactorily, there is always a need for improved devices and methods where the accuracy is increased and variations in the results are decreased. There is also a need for devices and methods where an estimate of the uncertainty can be provided.
Problems in the state of the art include variations in the deposition of reagents in the reaction zone on the assay device, binding of reagents, drying of the reagents, and reading of a signal from the assay device. Such variations, and possibly others, may introduce variations in the response, which is read from the analysis device.